Ding Qinfeng, Wang Yitong, Wang Tianyou, Zhang Chengyao, Yang Shengbing, Mao Lu, Cheng Yiyun, Li Yiwen, Lin Kaili
Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, China.
Department of Radiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
Bioact Mater. 2024 Oct 11;43:550-563. doi: 10.1016/j.bioactmat.2024.09.037. eCollection 2025 Jan.
Exploring highly efficient and cost-effective biomaterials for osteoarthritis (OA) treatment remains challenging, as current therapeutic strategies are difficult to eradicate the excessive reactive oxygen species (ROS) and nitric oxide (NO) at damaged sites. Tea polyphenol (TP) nanoparticles (NPs), a nature-inspired antioxidant in combination with 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a NO scavenger, could provide maximized positive therapeutic effects on OA by eradicating both ROS and NO. Notably, this combination not only improves the half-life of the TP monomer and the drug loading efficiency of carboxy-PTIO but also prevents nitrite from being harmful to tissue. Moreover, the protonation ability of carboxy-PTIO allows smart acid-responsive release in response to environmental pH, which provides conditioned treatment strategies for OA. In experiments, TP/PTIO NPs downregulated proinflammatory cytokine release via synergistic removal of ROS and NO and suppression of ROS/NF-κB and iNOS/NO/Caspase-3 signaling. For experiments, NPs were cross-linked with 4-arm-PEG-SH to form an injectable hydrogel system. The release of TP and carboxy-PTIO from the system efficiently prevents cartilage inflammation and damage via similar signaling pathways. Overall, the proposed system provides an efficient approach for OA therapy.
探索用于骨关节炎（OA）治疗的高效且经济高效的生物材料仍然具有挑战性，因为目前的治疗策略难以消除受损部位过量的活性氧（ROS）和一氧化氮（NO）。茶多酚（TP）纳米颗粒（NPs）是一种受自然启发的抗氧化剂，与NO清除剂2-（4-羧基苯基）-4,4,5,5-四甲基咪唑啉-1-氧基-3-氧化物（羧基-PTIO）相结合，可以通过消除ROS和NO对OA提供最大化的积极治疗效果。值得注意的是，这种组合不仅提高了TP单体的半衰期和羧基-PTIO的载药效率，还防止了亚硝酸盐对组织的危害。此外，羧基-PTIO的质子化能力允许其响应环境pH值进行智能酸响应释放，这为OA提供了有条件的治疗策略。在实验中，TP/PTIO NPs通过协同清除ROS和NO以及抑制ROS/NF-κB和iNOS/NO/Caspase-3信号通路，下调促炎细胞因子释放。在实验中，NPs与四臂聚乙二醇硫醇（4-arm-PEG-SH）交联形成可注射水凝胶系统。该系统中TP和羧基-PTIO的释放通过类似的信号通路有效防止软骨炎症和损伤。总体而言，所提出的系统为OA治疗提供了一种有效的方法。
